CD47 is a ubiquitously expressed immunoregulatory protein best known for its so-called 'don't eat me' function that prevents phagocytic removal of healthy cells by the immune system. Many types of cancer present high levels of this don't eat me signal on their surface, thereby disrupting anti-cancer immune responses. Based on this observation, CD47 has become a prominent target in the field of cancer immunotherapy. Indeed, pre-clinical studies have shown therapeutic benefit of anti-CD47 antibodies in solid cancers and most notably B-cell malignancies. However, CD47 is also involved in various other important cellular processes, such as angiogenesis, cancer cell death and regulation of T-cell immunity, which can be modulated via interactions with thrombospondin-1. The therapeutic outcome of CD47-targeted immunotherapy therefore relies on the combined effects of all these processes. Here we will review the various physiological functions of CD47 and their implications in cancer biology. Further, we will review ongoing efforts and provide perspectives for exploiting CD47 as an immunotherapeutic target in cancer....

PAX2 is the second member of the nine-member PAX gene family. PAX2's role begins as a developmental gene in late primitive streak stage embryos (Dressler et al., 1990). If PAX2 becomes expressed out of its normal context, its powerful functions as a transcription factor and epigenetic regulator (reviewed in Robson et al., 2006) can be recruited to the advantage of cancer cells (Robson et al., 2006; Li and Eccles, 2012). Normally PAX2 has key roles during embryogenesis, particularly in epithelial cell differentiation from mesenchyme (Rothenpieler and Dressler, 1993), such as in kidney development, and in mammary gland ductal morphogenesis (Silberstein et al., 2002). There is a requirement for the attenuation of PAX2 expression during development, particularly for the terminal differentiation of nephrogenic precursors (Dressler et al., 1993). Following the completion of development, PAX2 is capable of being re-expressed, such as in instances of nephrotoxicity or in other kidney damage (Cohen et al., 2007). In adult tissues, PAX2 is normally expressed in the pancreas (Zaiko et al., 2004), and also in subpopulations of nodal lymphocytes (Gilmore and Dewar, 2011). When expressed out of its normal context, expression of PAX2 is frequently observed in several cancer types (Robson et al., 2006). Expression of PAX2 has been linked with cell survival (Torban et al., 2000; Muratovska et al., 2003), cell migration and invasion (Buttiglieri et al., 2004), and mesenchyme-epithelial transition (MET) and epithelial-mesenchyme transition (EMT) (Doberstein et al., 2011)....

The FABP5 gene encodes a member of the fatty acid binding protein family which is also known as epidermal or cutaneous FABP. Overexpression of FABP5 is associated with a number of cancers including breast and prostate cancers, as well as psychiatric disorders and diabetes. FABP5 can bind retinoic acid as well as polyunsaturated and saturated fatty acids. Transport of FABP5 ligands such as arachidonic acid and retinoic acid to the nucleus is believed to activate the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR&beta;/&delta;)....

CHD6 is a chromatin remodeling protein characterized to play a role in transcriptional repression of genes and viruses. It occurs in a nuclear location as a component of a larger complex which associates with RNA Pol II. Mutations in CHD6 are associated with motor coordination defects, and development of cancers following substitutions and translocations....

ADAM23 belongs to the ADAM (A Disintegrin And Metalloproteinase domain) family of proteins. Members of this family present a common structural organization including metalloprotease, disintegrin, cystein-rich, epidermal growth factor-like, transmembrane and cytoplasmatic domains and are structurally related to snake venom disintegrins. ADAM23 has close similarity to ADAM11 and ADAM22; is highly expressed in the CNS, and is crucial for normal brain development. Mice homozygous for an insertional mutation that inactivates the gene are smaller than normal littermates, show delayed lung development, are lethal by postnatal day 14, and display severe tremor and ataxia. ADAM23 does not present metalloprotease activity and probably plays its biological role through the disintegrin domain. ADAM23 is involved in cell-cell adhesion and communication and cell-matrix modulation. The ADAM23 gene is frequently silenced by DNA promoter methylation in different types of solid cancers and epigenetic inactivation is associated with cancer progression, increased tumor cell mobility and reduced tumor cell proliferation....